Project Summary/Abstract The overarching theme of the proposed research program is to design modular organic receptors containing recognition elements that are optimized to bind anions in solution. The modularity allows for facile substitution of inherently fluorescent organic cores, recognition elements, linkers and functionality. This research will aid in the development of the next generation of molecular probes, sensors and binding agents for anions. The proposed receptors will also help provide a fundamental understanding of the structural role anions play in self-assembly and their interactions with electron- deficient aromatic rings. Long-term applications of this research include cellular and in vitro imaging of anions. The specific aims of the proposed research are: 1) to synthesize and to study a series of receptors for anions resulting from the proposed modular design strategy, 2) to study the modular receptors as fluorescent molecular probes for applications in chemical biology, and 3) to study the interaction of anions with electron-deficient aromatic rings and design recognition elements to exploit this emerging anion-binding motif. The modularity of the proposed design strategy allows for exploration of a variety of recognition motifs for anions, including electrostatic attractions, hydrogen bond interactions and attractions with electron-deficient arenes (anion-pi, CH---X- hydrogen bonds and weak-sigma complexes). This flexibility allows for the possibility of selectively binding anions that are challenging to target with traditional approaches. Core and linker substitution provides another approach to tuning the selectivity of the receptors by changing the shape and size of the binding pocket. The functionality of the receptors can also be adjusted to provide a route to make the molecules water-soluble or even permeable to cell membranes, as applications in cellular imaging are pursued once the solution chemistries are worked out. Studying new recognition motifs for anions, such as the emerging interaction between anions and electron-deficient arenes, requires understanding the basic science of manipulating these new theoretical binding motifs in order to design novel receptors. Applications from this research have the potential to be transferred to the design of new materials for remediation and sensing and may provide insights on the interaction between anions and biological substrates. The proposed research may also shed light on self-assembly processes in more complex biological systems. Therefore understanding anion binding on a molecular level is of paramount importance if one wishes to elucidate the roles of anions in the much more complicated biological processes.